Human variants annotation has been constantly evolving and is regarded as an indispensable step in genetic studies. Next generation sequencing (NGS) has significantly promoted the annotation work by genome-wide profiling of functional elements across human genome. With the urgent demands for identification of disease causal variants and personalized function loci, current annotation tools may be less comprehensive and user-friendly. Here, we introduced one-stop annotation web portal for human variations. We systematically applied many gene-based features and the latest NGS dataset to annotate all possible human single nucleotide variation (SNVs) from large-scale human genetic and genomic project, such as ENCODE and 1000 Genomes Projects. We applied several functional prediction algorithms to calculate the deleterious scores as well as related annotations for the variants that might affect different biological processes, including transcriptional gene regulation, alternative splicing, post-transcriptional regulation, translation, post-translational modification and natural selection.
1. Over 40 up-to-date annotation items for human single nucleotide variations;
2. Functional prediction for different types of variants;
3. Dynamic LD panel for both HapMap and 1000 Genomes Project populations;
4. Prioritization score and tree viewer based on variant functional model.
User can quickly identify the annotations of interested SNV by only requiring the chromosomal position (eg: 1:196659237) or dbSNP ID (eg: rs1061170);
User could input the query parameter in front page and annotation page;
User may select population options in annotation page such as individual panels and population.
SNVrap also support a RESTful query manner, like, http://jjwanglab.org/snvrap/snvrap/snvrap/quickrap/[chr]/[pos]
1. SNV summary information
--General Information: the SNV attributes and allele information;
--dbSNP Information: extract important SNP annotation from dbSNP 138;
--1000 Genomes Information: the 1000 Genomes Project allele information;
2. Gene-based annotation
The variant types and its surrounding genomic elements are the most direct and useful annotations for interpreting the putatively biological function that the variants affect. Conventionally, researchers frequently utilized RefGene (or KnownGene and Ensembl Gene) as the golden standard to locate variant attributes which indicate whether the investigated variant is resided in a gene body with the potential to disrupt the gene function. Attentions are specially focused on the non-synonymous mutation altering the protein domain and the splice mutation disrupting the transcript splicing. Recent RNA-Seq technology extends the discovery of new splicing events and novel transcripts, and the GENCODE project annotate all evidence-based gene features on entire human genome at high accuracy. In addition, annotations for many important non-coding RNAs (such as long non-coding RNA (lncRNA) and microRNA (miRNA)) are also an indispensable part in gene-based annotation.
--Long Noncoding RNAs
3. Knowledge-based annotation
The non-coding region in the human genome contains many important regulatory elements including promoter, enhancer and insulator. It is very important to annotate the variants effect in those function elements.
--MicroRNA Target (From TargetScan)
--Validated Human Enhancer
--Insulator (CTCF binding)
--HapMap eQTL Consensus
--ENCODE Epigenomic Signals
--ENCODE ChIP-Seq TF Binding Events
4. Functional Prediction annotation
Rather than simply linking annotations by a shared genomic location, researchers expect to know the exact function and the significance that variants exert. The functions of non-coding genetic variants are extensive in terms of the affected genomic region, and they can involve in almost all processes of gene regulation, from transcriptional to post-translational level.
--Transcription factors binding affinity
--MiRNA-target binding affinity
--Splicing site affection
--Non-synonymous SNP for protein function
--Synonymous SNP for translation efficiency
5. Evolutionary annotation
6. Disease relation annotation
--OMIM for inherited disorders
--GWAS for common phenotypes
--Clinical Phenotype/Disease Relation
--Cancer related annotation
7. External annotation
--dbPSHP: for positive selection
--Regulomedb: for regulatory variants
--HaploReg: for regulatory variants
--rSNPBase: for regulatory variants
SNVrap also provides a range of services for data retrieving about the annotation information and effect prediction of each variant in dbSNP using the SOAP interface. The WSDL for each service is available in the API tab. http://jjwanglab.org/snvrap/gwasrank/gwasrank/webservice#api_tab